Genotoxic studies in hypertensive and normotensive rats treated with amiodarone.
Amiodarone, a benzofuran derivative, is a very effective antiarrhythmic medication, but has potential to cause side effects. Although its cytotoxicity potential is very well-known, there are few reports about its genotoxicity effects. Since amiodarone has not been investigated in genotoxicity studies, and the spontaneously hypertensive rat (SHR) is a well-characterized model for hypertension, the aim of the present study was to perform cytogenetic analysis on chromosome aberrations in bone marrow cells of SHRs and normotensive Wistar-Kyoto rats (WKYs) that received oral amiodarone treatment for 4 weeks. Amiodarone activity was also monitored using electrocardiograms. The presence of bradycardia in amiodarone-treated rats confirmed that this drug was really active. Metaphase analysis on bone marrow cells showed that there were significant differences in total chromosomal damage and percentage abnormal metaphase between WKY and SHR negative controls. In the SHR negative control, the frequencies of basal chromosomal aberrations and abnormal metaphases were significantly higher (p<0.05). There were high numbers of chromosomal aberrations in all amiodarone-treated groups, compared with negative controls. In amiodarone-treated groups, the most frequent chromosomal aberration was chromatid breaks. More chromosomal aberrations were found in WKYs that received amiodarone, with a statistically significant difference in comparison with negative controls (p<0.05). However, in SHR rats there was no significant difference between the amiodarone and negative groups regarding chromosomal damage induction. These results showed that treatment with amiodarone was genotoxic in WKYs, but not in SHRs. Further studies are needed to confirm whether amiodarone is genotoxic or efficient and harmless, among humans undergoing therapy.
Almeida
Mara Ribeiro
MR
Depto. Ciências Biológicas, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil.
de Oliveira Lima
Estela
E
da Silva
Valdo José Dias
VJ
Campos
Mateus Gandra
MG
Antunes
Lusânia M G
LM
Salman
Ana Karina Dias
AK
Dias
Francisca L
FL
D000638:Amiodarone / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects; D002869:Chromosome Aberrations; D004249:DNA Damage; D005260:Female; D006973:Hypertension / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000889:Anti-Arrhythmia Agents; D000638:Amiodarone